Our ongoing work examines TCR gamma delta specificity and selection. We have identified a second class II MHC-specific allereactive gamma delta T cell line and found that it expresses the same V gamma J gamma/V delta J delta elements as a previously characterized alloreactive T cell line specific for a different set of class II MHC antigens. Three studies show that junctionally-encoded sequences influence gamma delta receptor specificity and are presumably important for antigen binding. We have extended our studies on TCR gamma delta development in the transgenic mouse model. We find that cyclosporine A fails to inhibit the development of gamma delta transgene bearing T cells, although it very efficiently blocks the antigen-induced activation of such cells. These studies should provide important insights into the mechanisms of T cell differentiation and signal transduction.